Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model

Abstract

Agents that destroy tumor cells and simultaneously boost host anti-tumor immunity are of keen interest in cancer therapy. In the present study, the effect of carnosol on anti-tumor immunity in a Balb/c mouse model of fibrosarcoma was evaluated. Carnosol was administered intraperitoneally daily (at 5 or 10 mg/kg/day, for 7 days) to tumor-bearing mice (i.e. 7 days after initial injection of tumor cells). Another group of tumor-bearing mice was treated with 20 mg cyclophosphamide/kg/d (positive control); a final group received vehicle only (vehicle control). After an initial measure on Day 0, tumor size was measured twice during the 7-day treatment period. One day after the final treatment with vehicle/carnosol (i.e. Day 7), the mice had their tumors measured and then were euthanized to permit their spleen and tumor to be harvested for isolation of, respectively, splenocytes and tumor-associated lymphocytes. Using these materials, spontaneous and mitogen-induced release of interleukin (IL)-4, IL-10, and interferon (IFN)-, lymphocyte proliferation, and the absolute numbers/relative percentages of splenic and tumor-associated T-regulatory (T reg ) and other T-lymphocyte sub-sets were evaluated. The results showed that carnosol at both doses significantly suppressed tumor growth and caused depletion of splenic and tumor-associated T reg cells. It also caused relative (vs control mouse cell values) decreases in splenocyte spontaneous/inducible production of IL-4 and IL-10 and increases in IFN and cell proliferation. Carnosol at either dose did not cause changes in the percentages of CD4 + or CD8 + lymphocytes in the spleen or in tumor-associated lymphocyte populations. The observed increases in IFN, decreases in IL-10 and IL-4 production, and reductions in splenic/tumor-associated T reg cell levels might be signs reflecting the potential anti-tumor activity of carnosol. Based on the findings here, it is asserted that carnosol is a likely candidate -after more complete toxicologic evaluation -for eventual use as an anti-cancer therapeutic.

Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis

“…In addition, a previous study showed that carnosol has anti-tumor capacity through prevention of Treg cell differentiation, decreasing IL-4 and IL-10 production, and enhancing IFN-γ secretion in tumor-associated lymphocyte populations ( 51 ). Tumor Tregs are a highly heterogeneous population that arises through disparate pathways and mediates immunologic effects by various means including soluble cytokines ( 52 ).…”

Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials

“…CS also led to a reduction in splenocyte delivery of IL-4 and IL-10, and an increase in Interferon (IFN) production. However, CS did not elicit modifications in the ratios of CD4+ or CD8+ lymphocytes in the spleen, or in tumor-associated lymphocyte cells [31].…”

Immunotoxicity induced in mice by subacute exposure to berberine

“…The doses of berberine used here were based on the study of Tsang et al (2013), demonstrating the anti-carcinogenic effects of doses of 5 or 10 mg berberine/kg in mice. The dose of cyclophosphamide was selected based on studies of Farsam et al (2011) and Rahnama et al (2014).…”

“…If the immune response is suppressed, the risks of infection and the formation of certain cancers are increased (Bendich, 1993). Over the past decades, natural compounds have become important candidates for investigation of the immunosuppression/stimulation of widely used natural compounds (Farsam et al, 2011;Noori et al, 2010;Rahnama et al, 2014). Since ancient times, people have sought cures for illness in nature.…”